Proinflammatory cytokines play a central role in infection-associated preterm labor. Infusion of IL-1a into rhesus monkey amniotic fluid (AF), in the absence of infection, results in increased uterine activity (UA), which is accompanied by elevated concentrations of AF cytokines and prostaglandins (PG's). Rhesus monkeys with INDO pretreatment were studied to clarify the role of PG's in elevated UA after IL-1 infusion. Maternal and fetal vascular catheters, intra-AF pressure (IAP), fetal ECG and myometrial EMG electrodes were implanted in 3 animals at 125 q 3 days of gestation. IL-1a was infused to each animal twice; 1) with INDO pretreatment (136 q 5 days of gestation), and 2) without INDO pretreatment (145 q 3 days of gestation). After stabilization, INDO (50mg, BID, PO) was administered for 5 days. On day 3, 10 g human recombinant IL-1a was infused into the AF over two hours (1100-1300h). UA was analyzed as hourly contraction area (HCA, mmHgysec/hr) during daylight hours before and 24 hrs after IL-1 infusion. AF samples were collected for PGE2, PGF2`, IL-1a, IL-6, and TNF` before and after the infusion. AF cytokines increased in all cases. UA was significantly elevated from baseline only in the absence of INDO pretreatment (*ANOVA, P<0.05). PGE2 was significantly elevated following both IL-1a infusions with a larger increase in the absence of INDO pretreatment (ANOVA, P<0.05). Two animals delivered within two days of the IL-1a infusion without INDO pretreatment. INDO Pretreatment No INDO Pretreatment UA (HCA, mmHg sec/hr) 285 q 50 5135 q 989* PGE2 (pg/ml) 569 q 410 7591 q 4109* mean q SEM PGF2` (pg/ml) 237 q 125 1480 q 659 *P<0.05 Following IL-1a infusion, 1) INDO blocked the development of UA; 2) INDO partially suppressed the increase in AF PGE2 and PGF2`. These results support the hypothesis that PGs, or other INDO-suppressible compounds, stimulate UA following IL-1a infusion in late-gestation rhesus monkeys.